Common variants in glyoxalase I do not increase chronic pancreatitis risk

Autoři: Tom Kaune aff001;  Marcus Hollenbach aff002;  Bettina Keil aff001;  Jian-Min Chen aff003;  Emmanuelle Masson aff003;  Carla Becker aff001;  Marko Damm aff001;  Claudia Ruffert aff001;  Robert Grützmann aff005;  Albrecht Hoffmeister aff002;  Rene H. M. te Morsche aff006;  Giulia Martina Cavestro aff007;  Raffaella Alessia Zuppardo aff007;  Adrian Saftoiu aff008;  Ewa Malecka-Panas aff009;  Stanislaw Głuszek aff010;  Peter Bugert aff011;  Markus M. Lerch aff012;  Frank Ulrich Weiss aff012;  Wen-Bin Zou aff013;  Zhuan Liao aff013;  Peter Hegyi aff014;  Joost PH Drenth aff006;  Jan Riedel aff001;  Claude Férec aff003;  Markus Scholz aff016;  Holger Kirsten aff016;  Andrea Tóth aff018;  Maren Ewers aff018;  Heiko Witt aff018;  Heidi Griesmann aff001;  Patrick Michl aff001;  Jonas Rosendahl aff001
Působiště autorů: Department of Internal Medicine I, Martin Luther University, Halle, Germany aff001;  Medical Department II–Gastroenterology, Hepatology, Infectious Diseases, Pulmonology, University of Leipzig Medical Center, Leipzig, Germany aff002;  Institut National de la Santé et de la Recherche Médicale (INSERM), U1078, Etablissement Français du Sang (EFS)–Bretagne, Faculté de Médecine et des Sciences de la Santé, Université de Bretagne Occidentale, Brest, France aff003;  Laboratoire de Génétique Moléculaire et d'Histocompatibilité, Centre Hospitalier Régional Universitaire (CHRU) Brest, Hôpital Morvan, Brest, France aff004;  Universitätsklinikum Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Chirurgische Klinik, Erlangen, Germany aff005;  Department of Gastroenterology and Hepatology, Radboud umc, Nijmegen, The Netherlands aff006;  Gastroenterology and Gastrointestinal Endoscopy Unit, Division of Experimental Oncology, Vita-Salute San Raffaele University, IRCCS Ospedale San Raffaele Scientific Institute, Milan, Italy aff007;  Department of Internal Medicine and Gastroenterology, University of Medicine and Pharmacy, Craiova, Romania aff008;  Department of Digestive Tract Diseases, Medical University of Łódź, Łódź, Poland aff009;  Faculty of Medicine and Health Sciences, Jan Kochanowski University, Kielce, Poland aff010;  Institute of Transfusion Medicine and Immunology, Medical Faculty Mannheim, Heidelberg University, German Red Cross Blood Service of Baden-Württemberg, Mannheim, Germany aff011;  Department of Medicine A, University Medicine Greifswald, Greifswald, Germany aff012;  Department of Gastroenterology, Changhai Hospital, Second Military Medical University, Shanghai Institute of Pancreatic Diseases, Shanghai, China aff013;  Institute for Translational Medicine and First Department of Internal Medicine, Medical School, University of Pécs, Pécs, Hungary aff014;  HAS-SZTE, Momentum Gastroenterology Multidisciplinary Research Group, Szeged, Hungary aff015;  Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig, Leipzig, Germany aff016;  LIFE- Leipzig Research Center for Civilization Diseases, University of Leipzig, Leipzig, Germany aff017;  Else Kröner-Fresenius-Zentrum für Ernährungsmedizin (EKFZ), Paediatric Nutritional Medicine, Technische Universität München (TUM), Freising, Germany aff018
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222927



Chronic pancreatitis (CP) may be caused by oxidative stress. An important source of reactive oxygen species (ROS) is the methylglyoxal-derived formation of advanced glycation endproducts (AGE). Methylglyoxal is detoxified by Glyoxalase I (GLO1). A reduction in GLO1 activity results in increased ROS. Single nucleotide polymorphisms (SNPs) of GLO1 have been linked to various inflammatory diseases. Here, we analyzed whether common GLO1 variants are associated with alcoholic (ACP) and non-alcoholic CP (NACP).


Using melting curve analysis, we genotyped a screening cohort of 223 ACP, 218 NACP patients, and 328 controls for 11 tagging SNPs defined by the SNPinfo LD TAG SNP Selection tool and the functionally relevant variant rs4746. For selected variants the cohorts were extended to up to 1,441 patient samples.


In the ACP cohort, comparison of genotypes for rs1937780 between patients and controls displayed an ambiguous result in the screening cohort (p = 0.08). However, in the extended cohort of 1,441 patients no statistically significant association was found for the comparison of genotypes (p = 0.11), nor in logistic regression analysis (p = 0.214, OR 1.072, 95% CI 0.961–1.196). In the NACP screening cohort SNPs rs937662, rs1699012, and rs4746 displayed an ambiguous result when patients were compared to controls in the recessive or dominant model (p = 0.08, 0.08, and 0.07, respectively). Again, these associations were not confirmed in the extended cohorts (rs937662, dominant model: p = 0.07, logistic regression: p = 0.07, OR 1.207, 95% CI 0.985–1.480) or in the replication cohorts for rs4746 (Germany, p = 0.42, OR 1.080, 95% CI 0.673–1.124; France, p = 0.19, OR 0.90, 95% CI 0.76–1.06; China, p = 0.24, OR 1.18, 95% CI 0.90–1.54) and rs1699012 (Germany, Munich; p = 0.279, OR 0.903, 95% CI 0.750–1.087).


Common GLO1 variants do not increase chronic pancreatitis risk.

Klíčová slova:

Alcoholics – German people – Human genetics – Molecular genetics – Pancreatitis – Polymerase chain reaction – Regression analysis – Variant genotypes


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